Apolipoproteins
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Apolipoproteins
Apolipoproteins are proteins that bind lipids (oil-soluble substances such as fats, cholesterol and fat soluble vitamins) to form lipoproteins. They transport lipids in blood, cerebrospinal fluid and lymph. The lipid components of lipoproteins are insoluble in water. However, because of their detergent-like ( amphipathic) properties, apolipoproteins and other amphipathic molecules (such as phospholipids) can surround the lipids, creating a lipoprotein particle that is itself water-soluble, and can thus be carried through body fluids (i.e., blood, lymph). In addition to stabilizing lipoprotein structure and solubilizing the lipid component, apolipoproteins interact with lipoprotein receptors and lipid transport proteins, thereby participating in lipoprotein uptake and clearance. They also serve as enzyme cofactors for specific enzymes involved in the metabolism of lipoproteins. Apolipoproteins are also exploited by hepatitis C virus (HCV) to enable virus entry, assembly, and tr ...
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Lipoproteins
A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, surrounded by a phospholipid outer shell, with the hydrophilic portions oriented outward toward the surrounding water and lipophilic portions oriented inward toward the lipid center. A special kind of protein, called apolipoprotein, is embedded in the outer shell, both stabilising the complex and giving it a functional identity that determines its role. Plasma lipoprotein particles are commonly divided into five main classes, based on size, lipid composition, and apolipoprotein content. They are, in increasing size order: HDL, LDL, IDL, VLDL and chylomicrons. Subgroups of these plasma particles are primary drivers or modulators of atherosclerosis. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are somet ...
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Apolipoprotein A1
Apolipoprotein AI (Apo-AI) is a protein that in humans is encoded by the ''APOA1'' gene. As the major component of high-density lipoprotein (HDL) particles, it has a specific role in lipid metabolism. Structure ''APOA1'' is located on chromosome 11, with its specific location being 11q23-q24. The gene contains 4 exons. The encoded apolipoprotein AI, is a 28.1 kDa protein composed of 243 amino acids; 21 peptides have been observed through mass spectrometry data. Due to alternative splicing, there exists multiple transcript variants of ''APOA1'', including at least one which encodes a Apo-AI preprotein. Function Apolipoprotein AI is the major protein component of high density lipoprotein (HDL) particles in plasma. Chylomicrons secreted from the intestinal enterocyte also contain Apo-AI, but it is quickly transferred to HDL in the bloodstream. The protein, as a component of HDL particles, enables efflux of fat molecules by accepting fats from within cells (including macro ...
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Apolipoprotein E
Apolipoprotein E (Apo-E) is a protein involved in the metabolism of fats in the body of mammals. A subtype is implicated in Alzheimer's disease and cardiovascular diseases. It is encoded in humans by the gene ''APOE''. Apo-E belongs to a family of fat-binding proteins called apolipoproteins. In the circulation, it is present as part of several classes of lipoprotein particles, including chylomicron remnants, VLDL, IDL, and some HDL. Apo-E interacts significantly with the low-density lipoprotein receptor (LDLR), which is essential for the normal processing (catabolism) of triglyceride-rich lipoproteins. In peripheral tissues, Apo-E is primarily produced by the liver and macrophages, and mediates cholesterol metabolism. In the central nervous system, Apo-E is mainly produced by astrocytes and transports cholesterol to neurons via Apo-E receptors, which are members of the low density lipoprotein receptor gene family. Apo-E is the principal cholesterol carrier in the brain. Apo ...
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Apolipoprotein B
Apolipoprotein B (ApoB) is a protein that in humans is encoded by the gene. Its measurement is commonly used to detect the risk of Atherosclerosis, atherosclerotic Coronary artery disease, cardiovascular disease. Isoforms The protein occurs in the blood plasma, plasma in two main isoforms, ApoB48 and ApoB100. The first is synthesized exclusively by the small intestine, the second by the liver. ApoB-100 is the largest of the apoB group of proteins, consisting of 4563 amino acids, including a 27-amino acid signal peptide and a 4536-amino acid mature protein. Both isoforms are coded by ''APOB'' and by a single mRNA transcript larger than 16 kb. ApoB48 is generated when a stop codon (UAA) at residue 2153 is created by RNA editing. There appears to be a ''trans''-acting tissue-specific splicing gene that determines which isoform is ultimately produced. Alternatively, there is some evidence that a ''cis''-acting element several thousand base pair, bp upstream determines which isof ...
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High-density Lipoprotein
High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are typically composed of 80–100 proteins per particle (organized by one, two or three ApoA). HDL particles enlarge while circulating in the blood, aggregating more fat molecules and transporting up to hundreds of fat molecules per particle. HDL particles are commonly referred to as "good cholesterol", because they transport fat molecules out of artery walls, reduce macrophage accumulation, and thus help prevent or even regress atherosclerosis. Overview Lipoproteins are divided into five subgroups, by density/size (an inverse relationship), which also correlates with function and incidence of cardiovascular events. Unlike the larger lipoprotein particles, which deliver fat molecules to cells, HDL particles remove fat molecules from cells. ...
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APOA4
Apolipoprotein A-IV (also known as apoA-IV, apoAIV, or apoA4) is plasma protein that is the product of the human gene ''APOA4''. Gene APOA4 resides on chromosome 11 in close linkage to APOA1 and APOC3. APOA4 contains 3 exons separated by two introns, and is polymorphic, although most of the reported sequence polymorphisms occur in exon 3. The best validated and studied non-synonymous SNPs are a glutamine → histidine substitution at codon 360 and a threonine → serine substitution at codon 347; a sequence polymorphism has also been identified in the 3'UTR of the third exon. Intra-species comparative gene sequence analysis suggests that the APOA4 gene arose from APOA1 by gene duplication approximately 270 MYA. Function The primary translation product of the APOA4 gene is a 396-residue preprotein, which undergoes proteolytic processing to yield apo A-IV, a 376-residue mature O-linked glycoprotein. In most mammals, including humans, apo A-IV synthesis is confined to the ...
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Apolipoprotein D
Apolipoprotein D (ApoD) is a protein that in humans is encoded by the ''APOD'' gene. Unlike other lipoproteins, which are mainly produced in the liver, apolipoprotein D is mainly produced in the brain and testes. It is a 29 kDa glycoprotein discovered in 1963 as a component of the high-density lipoprotein (HDL) fraction of human plasma. It is the major component of human mammary cyst fluid. The human gene encoding it was cloned in 1986 and the deduced protein sequence revealed that ApoD is a member of the lipocalin family, small hydrophobic molecule transporters. ApoD is 169 amino acids long, including a secretion peptide signal of 20 amino acids. It contains two glycosylation sites (aspargines 45 and 78) and the molecular weight of the mature protein varies from 20 to 32 kDa (see figure 1). The resolved tertiary structure shows that ApoD is composed of 8 anti-parallel β-strands forming a hydrophobic cavity capable of receiving different ligands. ApoD also contains 5 cysteine resi ...
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Cholesterol
Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all animal Cell (biology)#Eukaryotic cells, cells and is an essential structural and cholesterol signaling, signaling component of animal cell membranes. In vertebrates, hepatocyte, hepatic cells typically produce the greatest amounts. In the brain, astrocytes produce cholesterol and transport it to neurons. It is absent among prokaryotes (bacteria and archaea), although there are some exceptions, such as ''Mycoplasma'', which require cholesterol for growth. Cholesterol also serves as a Precursor (chemistry), precursor for the biosynthesis of steroid hormones, bile acid and vitamin D. Elevated levels of cholesterol in the blood, especially when bound to low-density lipoprotein (LDL, often referred to as "bad cholesterol"), may increase the risk of ...
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Hepatitis C Virus
The hepatitis C virus (HCV) is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family ''Flaviviridae''. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer ( hepatocellular carcinoma, abbreviated HCC) and lymphomas in humans. Taxonomy The hepatitis C virus belongs to the genus '' Hepacivirus'', a member of the family ''Flaviviridae''. Before 2011, it was considered to be the only member of this genus. However a member of this genus has been discovered in dogs: canine hepacivirus. There is also at least one virus in this genus that infects horses. Several additional viruses in the genus have been described in bats and rodents. Structure The hepatitis C virus particle consists of a lipid membrane envelope that is 55 to 65 nm in diameter. Two viral envelope glycoproteins, E1 and E2, are embedded in the lipid envelope. They take part in viral attachment and entry into the cell. Within the e ...
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Receptor (biochemistry)
In biochemistry and pharmacology, receptors are chemical structures, composed of protein, that receive and Signal_transduction, transduce signals that may be integrated into biological systems. These signals are typically chemical messengers which bind to a receptor and produce physiological responses, such as a change in the electrophysiology, electrical activity of a cell. For example, GABA, an inhibitory neurotransmitter, inhibits electrical activity of neurons by binding to GABAA receptor, GABA receptors. There are three main ways the action of the receptor can be classified: relay of signal, amplification, or integration. Relaying sends the signal onward, amplification increases the effect of a single ligand (biochemistry), ligand, and integration allows the signal to be incorporated into another biochemical pathway. Receptor proteins can be classified by their location. Cell surface receptors, also known as transmembrane receptors, include ligand-gated ion channels, G prote ...
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Low-density Lipoprotein
Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall density naming convention), very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDL delivers fat molecules to Cell (biology), cells. LDL has been associated with the progression of atherosclerosis. Overview Lipoproteins transfer lipids (fats) around the body in the extracellular fluid, making fats available to body cells for receptor-mediated endocytosis. Lipoproteins are complex particles composed of multiple proteins, typically 80–100 proteins per particle (organized by a single apolipoprotein B for LDL and the larger particles). A single LDL particle is about 22–27.5 nanometers in diameter, typically transporting 3,000 to 6,000 fat molecules per part ...
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Reverse Cholesterol Transport
Reverse cholesterol transport (RCT) is a multistep process comprising removal of excess cholesterol from cells in the body and delivery to the liver for excretion into the small intestine. Enhancing reverse cholesterol transport is considered a potential strategy for preventing and treating atherosclerosis and associated diseases such as cardiovascular disease and stroke. Atherosclerosis is caused by the build-up in arterial blood vessels of atherosclerotic plaques. These consist mostly of foam cells, which are macrophages overloaded with cholesterol and other lipids. Foam cells and other cells in peripheral tissues can hand over their excess cholesterol to high-density lipoprotein (HDL) particles. These will transport the cholesterol via the lymph and then the blood stream to the liver, from where it will be excreted with bile into the small intestine. Reverse cholesterol transport thereby works against the build-up of atherosclerotic plaques from dying foam cells. In more deta ...
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